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The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study

By Kurt Taylor, Ahmed Elhakeem, Johanna Lucia Thorbjørnsrud Nader, Tiffany Yang, Elena Isaevska, Lorenzo Richiardi, Tanja Vrijkotte, Angela Pinot de Moira, Deirdre M Murray, Daragh Finn, Dan Mason, John Wright, Sam Oddie, Nel Roeleveld, Jennifer R Harris, Anne-Marie Nybo Andersen, Massimo Caputo, Deborah A. Lawlor

Posted 30 Sep 2020
medRxiv DOI: 10.1101/2020.09.29.20203786

BackgroundCongenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and ResultsSeven European birth cohorts including 232,390 offspring (2,469 CHD cases [1.1%]) were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression and combined estimates using a fixed-effects meta-analysis. Analyses of BMI categories resulted in similar increased odds of CHD in overweight (mothers OR: 1.15 (1.01, 1.31) and fathers 1.10 (0.96, 1.27)) and obesity (mothers OR: 1.12 (0.93, 1.36) and fathers 1.16 (0.90, 1.50)). The association of mean BMI with CHD was null. Maternal smoking was associated with increased odds of CHD (OR: 1.11 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The difference increased when removing offspring with genetic/chromosomal defects (mothers OR: 1.15 (1.01, 1.32) and fathers 0.93 (0.83, 1.05)). The positive association with maternal pregnancy smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal (OR: 1.16 (0.52, 2.58)) and paternal (OR: 1.23 (0.74, 2.06)) moderate/heavy pregnancy alcohol consumption were similar. ConclusionsWe found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for why smoking cessation is important during pregnancy.

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